Lysine-specific demethylase 2A (KDM2A) also known as F-box and leucine-rich repeat protein 11 (FBXL11) is an enzyme that in humans is encoded by the KDM2Agene.[5][6][7] KDM2A is a member of the superfamily of alpha-ketoglutarate-dependent hydroxylases, which are non-haem iron-containing proteins.
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least 6 highly degenerated leucine-rich repeats.[7]
FBXL11/KDM2A is a histone H3 lysine 36 demethylase enzyme. The enzymatic activity of FBXL11/KDM2A relies on a conserved JmjC domain in the N-terminus of the protein that co-ordinates iron and alphaketoglutarate to catalyze demethylation via a hydroxylation based mechanism.[8] It has recently been demonstrated that a ZF-CxxC DNA binding domain within FBXL11/KDM2A has the capacity to interact with non-methylated DNA and this domain targets FBXL11/KDM2A to CpG island regions of the genome where it specifically removes histone H3 lysine 36 methylation.[9] This mechanism acts to create a chromatin environment at CpG islands that highlights these regulatory elements and differentiates them from non-regulatory regions in large complex mammalian genomes. In a study in mouse hepatocytes, this gene was shown to regulate hepatic gluconeogenesis.[10]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000173120 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000054611 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032.
^Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Dec 1999). "A family of mammalian F-box proteins". Curr Biol. 9 (20): 1180–2. Bibcode:1999CBio....9.1180W. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037. S2CID 14341845.
^ ab"Entrez Gene: FBXL11 F-box and leucine-rich repeat protein 11".
^Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (February 2006). "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811–6. Bibcode:2006Natur.439..811T. doi:10.1038/nature04433. PMID 16362057. S2CID 4415889.
^Pan D, Mao C, Zou T, Yao AY, Cooper MP, Boyartchuk V, Wang YX (2012). "The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis". PLOS Genetics. 8 (6): e1002761. doi:10.1371/journal.pgen.1002761. PMC3375226. PMID 22719268.
Further readingedit
Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M (1999). "Identification of a family of human F-box proteins". Curr. Biol. 9 (20): 1177–9. Bibcode:1999CBio....9.1177C. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035. S2CID 7467493.
Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (2001). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family". Genomics. 67 (1): 40–7. doi:10.1006/geno.2000.6211. PMID 10945468.
Hattori A, Okumura K, Nagase T, Kikuno R, Hirosawa M, Ohara O (2001). "Characterization of long cDNA clones from human adult spleen". DNA Res. 7 (6): 357–66. doi:10.1093/dnares/7.6.357. PMID 11214971.
Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (2004). "M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4419–24. Bibcode:2004PNAS..101.4419W. doi:10.1073/pnas.0307700101. PMC384762. PMID 15070733.
Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC442148. PMID 15231748.
Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83. Bibcode:2005Natur.433...77A. doi:10.1038/nature03207. PMID 15635413. S2CID 4344740.
Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006). "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811–6. Bibcode:2006Natur.439..811T. doi:10.1038/nature04433. PMID 16362057. S2CID 4415889.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
kdm2a, lysine, specific, demethylase, also, known, leucine, rich, repeat, protein, fbxl11, enzyme, that, humans, encoded, gene, member, superfamily, alpha, ketoglutarate, dependent, hydroxylases, which, haem, iron, containing, proteins, available, structurespd. Lysine specific demethylase 2A KDM2A also known as F box and leucine rich repeat protein 11 FBXL11 is an enzyme that in humans is encoded by the KDM2A gene 5 6 7 KDM2A is a member of the superfamily of alpha ketoglutarate dependent hydroxylases which are non haem iron containing proteins KDM2AAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes2YU1 2YU2 4BBQIdentifiersAliasesKDM2A CXXC8 FBL11 FBL7 FBXL11 JHDM1A LILINA lysine demethylase 2AExternal IDsOMIM 605657 MGI 1354736 HomoloGene 56564 GeneCards KDM2AGene location Human Chr Chromosome 11 human 1 Band11q13 2Start67 119 263 bp 1 End67 258 082 bp 1 Gene location Mouse Chr Chromosome 19 mouse 2 Band19 19 AStart4 364 447 bp 2 End4 448 313 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inamniotic fluidgerminal epitheliumtibiasural nervenipplevisceral pleuraparietal pleurabone marrow cellsthymuspylorusTop expressed inhandaortic valveascending aortalipthymusfootesophagusinternal carotid arterycerebellar cortexsupraoptic nucleusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionDNA binding oxidoreductase activity zinc ion binding dioxygenase activity metal ion binding histone demethylase activity protein binding histone H3 methyl lysine 36 demethylase activity DNA binding transcription factor activity RNA polymerase II specificCellular componentnucleoplasm nucleusBiological processdouble strand break repair via nonhomologous end joining regulation of transcription DNA templated histone H3 K36 demethylation transcription DNA templated chromatin organization regulation of transcription by RNA polymerase II negative regulation of transcription by competitive promoter binding circadian regulation of gene expression regulation of circadian rhythm rhythmic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez22992225876EnsemblENSG00000173120ENSMUSG00000054611UniProtQ9Y2K7P59997RefSeq mRNA NM 001256405NM 012308NM 001001984RefSeq protein NP 001243334NP 036440NP 001001984Location UCSC Chr 11 67 12 67 26 MbChr 19 4 36 4 45 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseFunction editThis gene encodes a member of the F box protein family which is characterized by an approximately 40 amino acid motif the F box The F box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs SKP1 cullin F box which function in phosphorylation dependent ubiquitination The F box proteins are divided into 3 classes Fbws containing WD 40 domains Fbls containing leucine rich repeats and Fbxs containing either different protein protein interaction modules or no recognizable motifs The protein encoded by this gene belongs to the Fbls class and in addition to an F box contains at least 6 highly degenerated leucine rich repeats 7 FBXL11 KDM2A is a histone H3 lysine 36 demethylase enzyme The enzymatic activity of FBXL11 KDM2A relies on a conserved JmjC domain in the N terminus of the protein that co ordinates iron and alphaketoglutarate to catalyze demethylation via a hydroxylation based mechanism 8 It has recently been demonstrated that a ZF CxxC DNA binding domain within FBXL11 KDM2A has the capacity to interact with non methylated DNA and this domain targets FBXL11 KDM2A to CpG island regions of the genome where it specifically removes histone H3 lysine 36 methylation 9 This mechanism acts to create a chromatin environment at CpG islands that highlights these regulatory elements and differentiates them from non regulatory regions in large complex mammalian genomes In a study in mouse hepatocytes this gene was shown to regulate hepatic gluconeogenesis 10 References edit a b c GRCh38 Ensembl release 89 ENSG00000173120 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000054611 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Nagase T Ishikawa K Suyama M Kikuno R Hirosawa M Miyajima N Tanaka A Kotani H Nomura N Ohara O Jul 1999 Prediction of the coding sequences of unidentified human genes XIII The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro DNA Res 6 1 63 70 doi 10 1093 dnares 6 1 63 PMID 10231032 Winston JT Koepp DM Zhu C Elledge SJ Harper JW Dec 1999 A family of mammalian F box proteins Curr Biol 9 20 1180 2 Bibcode 1999CBio 9 1180W doi 10 1016 S0960 9822 00 80021 4 PMID 10531037 S2CID 14341845 a b Entrez Gene FBXL11 F box and leucine rich repeat protein 11 Tsukada Y Fang J Erdjument Bromage H Warren ME Borchers CH Tempst P Zhang Y February 2006 Histone demethylation by a family of JmjC domain containing proteins Nature 439 7078 811 6 Bibcode 2006Natur 439 811T doi 10 1038 nature04433 PMID 16362057 S2CID 4415889 Blackledge NP Zhou JC Tolstorukov MY Farcas AM Park PJ Klose RJ Apr 2010 CpG islands recruit a histone H3 lysine 36 demethylase Molecular Cell 38 2 179 90 doi 10 1016 j molcel 2010 04 009 PMC 3098377 PMID 20417597 Pan D Mao C Zou T Yao AY Cooper MP Boyartchuk V Wang YX 2012 The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis PLOS Genetics 8 6 e1002761 doi 10 1371 journal pgen 1002761 PMC 3375226 PMID 22719268 Further reading editNakajima D Okazaki N Yamakawa H Kikuno R Ohara O Nagase T 2003 Construction of expression ready cDNA clones for KIAA genes manual curation of 330 KIAA cDNA clones DNA Res 9 3 99 106 doi 10 1093 dnares 9 3 99 PMID 12168954 Cenciarelli C Chiaur DS Guardavaccaro D Parks W Vidal M Pagano M 1999 Identification of a family of human F box proteins Curr Biol 9 20 1177 9 Bibcode 1999CBio 9 1177C doi 10 1016 S0960 9822 00 80020 2 PMID 10531035 S2CID 7467493 Ilyin GP Rialland M Pigeon C Guguen Guillouzo C 2001 cDNA cloning and expression analysis of new members of the mammalian F box protein family Genomics 67 1 40 7 doi 10 1006 geno 2000 6211 PMID 10945468 Hattori A Okumura K Nagase T Kikuno R Hirosawa M Ohara O 2001 Characterization of long cDNA clones from human adult spleen DNA Res 7 6 357 66 doi 10 1093 dnares 7 6 357 PMID 11214971 Watanabe N Arai H Nishihara Y Taniguchi M Watanabe N Hunter T Osada H 2004 M phase kinases induce phospho dependent ubiquitination of somatic Wee1 by SCFbeta TrCP Proc Natl Acad Sci U S A 101 13 4419 24 Bibcode 2004PNAS 101 4419W doi 10 1073 pnas 0307700101 PMC 384762 PMID 15070733 Colland F Jacq X Trouplin V Mougin C Groizeleau C Hamburger A Meil A Wojcik J Legrain P Gauthier JM 2004 Functional proteomics mapping of a human signaling pathway Genome Res 14 7 1324 32 doi 10 1101 gr 2334104 PMC 442148 PMID 15231748 Andersen JS Lam YW Leung AK Ong SE Lyon CE Lamond AI Mann M 2005 Nucleolar proteome dynamics Nature 433 7021 77 83 Bibcode 2005Natur 433 77A doi 10 1038 nature03207 PMID 15635413 S2CID 4344740 Tsukada Y Fang J Erdjument Bromage H Warren ME Borchers CH Tempst P Zhang Y 2006 Histone demethylation by a family of JmjC domain containing proteins Nature 439 7078 811 6 Bibcode 2006Natur 439 811T doi 10 1038 nature04433 PMID 16362057 S2CID 4415889 Olsen JV Blagoev B Gnad F Macek B Kumar C Mortensen P Mann M 2006 Global in vivo and site specific phosphorylation dynamics in signaling networks Cell 127 3 635 48 doi 10 1016 j cell 2006 09 026 PMID 17081983 S2CID 7827573 Portal nbsp Biology nbsp This article on a gene on human chromosome 11 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title KDM2A amp oldid 1217024567, wikipedia, wiki, book, books, library,
